Tularemia is a zoonotic disease caused by Francisella
tularensis, a fastidious, gram-negative coccobacillus that infects
vertebrates, especially rabbits and rodents. In humans, tularemia is classified
into six major syndromes: ulceroglandular (the most common form), glandular,
typhoidal, oculoglandular, oropharyngeal, and pneumonic. The case-fatality
rate among humans can reach 30%-60% in untreated typhoidal cases.1 Although
bites from ticks and handling infected animals are considered the most common
modes of tularemia transmission in the United States,2,3,4 the
disease also is spread through ingestion of contaminated food or water, inhalation,
and insect bites.1,2,3,4,5 During 2001-2003, Wyoming experienced
an increase in reported human cases of tularemia. This report describes the
subsequent investigation by the Wyoming Department of Health (WDH), which
indicated that (1) insect bites (particularly from deerflies and other horseflies)
were the most commonly reported likely mode of transmission, and (2) the increase
in cases was geographically and temporally associated with an outbreak of
tularemia among rabbits in southwestern Wyoming. To obtain a timely diagnosis
and provide information on appropriate preventive measures, health-care providers
and public health officials should have knowledge of the local epidemiology
of tularemia, particularly regarding modes of transmission and resultant clinical
syndromes.

Tularemia is a reportable disease in Wyoming and is designated as a
nationally notifiable disease. In this investigation, a case was defined as
a confirmed or probable case of tularemia reported to WDH during 1990-2003.
A confirmed case was defined as a clinically compatible case with confirmatory
laboratory results, which might include either isolation of F. tularensis in a clinical specimen or a fourfold or greater change
in antibody titer. A probable case was defined as a clinically compatible
case with laboratory results indicative of infection, which might include
either a single elevated antibody titer or detection of F. tularensis in a clinical specimen by immunohistochemistry or immunofluorescence.6 A case of insect-borne tularemia was defined as tularemia that occurred
within 14 days of a fly, flea, or other insect bite in a patient with no other
known exposures, including tick bites and handling of infected animal tissues.
Patient interviews, medical record reviews, or reviews of archived follow-up
forms were conducted for each case. In this report, location refers to the
geographic location of exposure, except where a definite exposure location
was not reported (four cases); in those instances, location refers to place
of residence.

During 2001-2003, a total of 11 cases (six confirmed; five probable)
of tularemia were reported in Wyoming, for an average of 3.7 cases per year.
In contrast, 10 cases (seven confirmed; three probable) were reported during
1990-2000, for an average of 0.9 cases per year.

Of the 11 cases reported during 2001-2003, nine (82%) were in male patients.
Six (55%) of the tularemia cases were the ulceroglandular type, and all included
insect bites as the likely mode of transmission. Two cases (18%) were the
typhoidal type, and the remaining three cases were the glandular, oculoglandular,
and pneumonic types (9% each). No deaths were reported.

In seven (64%) cases, insect bites (from deerflies or other horseflies
in six cases; flies and/or fleas in one case) were determined to be the most
likely mode of transmission. Six of these patients had ulceroglandular tularemia;
one patient had typhoidal tularemia. Median age of persons for whom insect
bites were the likely mode of transmission was 40 years (range: 18 months–68
years). Median age of those with other modes of transmission was 53 years
(range: 40-70 years). Likely modes of transmission in the other four cases
were infected rabbit exposure (one), infected sheep exposure (one), and unknown
(two). In contrast, during 1990-2000, no cases were linked to insect bites.
The likely modes of transmission in cases during 1990-2000 were ticks (four),
rabbits (three), sheep (one), and unknown (two). Eight (73%) of the 11 cases
reported during 2001-2003 were reported from counties in southwestern Wyoming
(Sweetwater [five], Lincoln [two], and Uinta [one]); the remaining three (27%)
were distributed among counties elsewhere in the state (one case each in Fremont,
Park, and Teton counties). The F. tularensis isolates
from the six confirmed cases that occurred during 2001-2003 were further classified
into types A or B. Five of these typed isolates were from cases in the southwestern
region of the state, where an epizootic among rabbits was thought to have
occurred; all five were classified as type A. One isolate from the northwestern
region was classified as type B.

In October 2003, WDH was informed that two ill rabbits from the Seedskadee
National Wildlife Refuge in southwestern Wyoming collected in the summer and
early fall of 2003 tested positive for tularemia. Refuge personnel reported
an increase in the number of dead or ill rabbits during the summers of 2002
and 2003.

The organism that causes tularemia was isolated from humans in 1919
during an investigation of the cause of deerfly fever in Utah. Laboratory
studies conducted at the time confirmed that deerflies (Chrysops discalis) can transmit the organism among animals. Despite
this original association with biting flies, most cases in the United States
are attributed to noninsect exposures, especially tick bites and contact with
infected animal tissues.2,3 This report illustrates how the epidemiology
of tularemia can be region-dependent and change over time. Because proper
diagnosis and treatment of tularemia relies on a high index of suspicion and
clinical presentation is related to the method of acquisition (e.g., development
of ulceroglandular tularemia after an insect bite),1,2 health-care
providers should understand the local epidemiology of tularemia. On the basis
of this knowledge, public health officials can recommend locally appropriate
prevention and control measures, such as wearing gloves when handling dead
animals (particularly rabbits and rodents); cooking game meat thoroughly;
avoiding bites of ticks, flies, and mosquitoes by using insect repellent and
wearing long clothing; and avoiding drinking untreated water. In addition,
a local epizootic of tularemia might correlate with an increase in human cases
and should heighten awareness that tularemia might be a possibility in clinically
compatible cases.

In this outbreak, insect bites accounted for 64% of recent human cases.
These cases were geographically and temporally associated with an epizootic
among rabbits in southwestern Wyoming. Subtyping data revealed that all isolates
from humans in this area were type A, the subtype most commonly associated
with rabbits,7 thereby supporting a likely connection between these
events. Deerflies have been implicated in two previous outbreaks of tularemia;
in both instances, a concomitant epizootic among rabbits was observed.5 Whereas enzootic cycles of tularemia might not be apparent, epizootics
with die-off of animal hosts might correlate with increases of tularemia in
humans.5

The findings in this report are subject to at least two limitations.
First, the likely modes of transmission in the recent Wyoming cases were determined
from the histories reported by patients and therefore might be limited by
recall bias. Second, other unrecognized modes of transmission might have coincided
with the exposures that were reported.

As with many other diseases, proper diagnosis and treatment of tularemia
relies on a high index of suspicion. Laboratory diagnosis of F. tularensis depends on the laboratory being notified that tularemia
is a clinical possibility. Identification of the organism is important because
it is often resistant to antibiotics commonly used empirically for skin and
systemic infections.1,8